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Clinical Trial
. 2015 Apr;30(4):677-85.
doi: 10.1007/s00467-014-2989-y. Epub 2014 Oct 28.

Pediatric reference ranges for acute kidney injury biomarkers

Michael R Bennett  1 , Edward Nehus, Christopher Haffner, Qing Ma, Prasad Devarajan
Affiliations
Clinical Trial

Pediatric reference ranges for acute kidney injury biomarkers

Michael R Bennett et al. Pediatr Nephrol. 2015 Apr.

Abstract

Background: Novel urinary biomarkers are useful for the prediction of acute kidney injury (AKI). Most promising are the urine markers NGAL, IL-18, KIM-1, and LFABP. Each of these has shown considerable promise diagnosing AKI earlier than serum creatinine (Scr) using disease controls. We set out to determine reference levels of these markers in a healthy pediatric population.

Methods: Urine was collected from 368 healthy children and assayed for NGAL, IL-18, KIM-1, and LFABP using commercially available kits or assay materials. Analysis of biomarkers by linear regression and according to age groups (3-<5 years; 5-<10; 10-<15; 15-<18) was performed to determine if biomarker levels differed with age and gender.

Results: Median values were: NGAL (6.6 ng/ml; IQR 2.8-17), IL-18 (21.6 pg/ml; IQR 13.6-32.9), KIM-1 (410 pg/ml; IQR 226-703), LFABP (3.4 ng/ml; IQR 1.6-6.0). Significant gender differences were found with NGAL and IL-18 and significant age differences were found with all markers. 95th percentile values for each marker varied with age and gender greater than median values.

Conclusions: This is the largest pediatric reference range study for the urinary measurement of NGAL, IL-18, KIM-1, and LFABP and highlights age and gender differences in these markers. This information is essential for rational interpretation of studies and clinical trials utilizing these emerging AKI biomarkers.

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Figures

Fig. 1
Fig. 1
Gender differences in biomarker values by age group. The four graphs represent median values for each individual biomarker in males and females, separated by age group. Error bars indicate 75th percentile. Asterisk represents a significant difference in gender values in that specific group. NGAL neutrophil gelatinase associated lipocalin, IL-18 interleukin 18, LFABP liver fatty acid binding protein, KIM-1 kidney injury molecule 1
Fig. 2
Fig. 2
Age-related differences in biomarker values. The four graphs represent median values for each individual biomarker separated by age group. Error bars indicate 75th percentile. The asterisk represents a significant difference and horizontal lines connect the significantly higher group to the groups they are different than, with drop lines indicating those groups. NGAL neutrophil gelatinase associated lipocalin, IL-18 interleukin 18, LFABP liver fatty acid binding protein, KIM-1 kidney injury molecule 1
Fig. 3
Fig. 3
Graphical distribution of biomarker values by age with best-fit regression line. Each dot in the scatter plot represents the raw biomarker value for a specific participant, plotted on a logarithmic scale. NGAL neutrophil gelatinase-associated lipocalin, IL-18 interleukin 18, LFABP liver fatty acid binding protein, KIM-1 kidney injury molecule 1
See this image and copyright information in PMC

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